| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
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| Other Sizes |
| Targets |
PEGs Alkyl/ether
PROTAC Linkers. |
|---|---|
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
As a linker molecule, DBCO-PEG8-NHS ester itself has no intrinsic biological activity; it serves as a structural connector to join a target protein ligand and an E3 ubiquitin ligase ligand in PROTAC synthesis. The DBCO group is a strained alkyne that reacts specifically and rapidly with azide groups via SPAAC without the need for a copper catalyst. This copper-free click chemistry is bioorthogonal and biocompatible, making it ideal for conjugations in the presence of cells or biological samples. The NHS ester group allows for conjugation to primary amine-containing ligands via amide bond formation under mild conditions. The PEG8 spacer provides a long, hydrophilic, and flexible connection between the two reactive groups, which can facilitate the formation of productive ternary complexes. The orthogonal functional groups enable stepwise conjugation to two different ligands. |
| ln Vivo |
No specific in vivo activity has been reported for this linker alone; its activity is derived from the final PROTAC molecule after conjugation with appropriate ligands. The in vivo efficacy of a complete PROTAC is determined in animal models.
|
| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. As a synthetic intermediate, its quality is typically confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥98%. The DBCO group can be characterized by its characteristic UV absorption (around 300 nm). The NHS ester group can be characterized by its characteristic chemical shifts in NMR spectroscopy and by its reactivity with primary amines. The IUPAC name is (2,5-dioxopyrrolidin-1-yl) 1-(11,12-didehydrodibenzo[b,f]azocin-5(6H)-yl)-1-oxo-3,6,9,12,15,18,21,24,27-nonaoxa-2-azatetraconta-31,33,35,37,39-pentaen-41-oate.
|
| Cell Assay |
N/A; this linker is not tested alone in cell-based assays. It is used as a building block for constructing PROTACs. In a typical synthesis, the NHS ester is reacted with a primary amine-containing ligand (e.g., an E3 ligase ligand) in a buffer such as PBS (pH 7.4) at room temperature for 1-2 hours. The DBCO group is then reacted with an azide-containing ligand (e.g., a target protein ligand) via SPAAC in a copper-free click reaction at room temperature for 1-4 hours. The resulting PROTAC is then tested in cells for target degradation activity. The PEG8 spacer provides a long, flexible connection that may be optimal for target-E3 ligase pairs that require a long distance between binding sites.
|
| Animal Protocol |
N/A; no animal studies are performed with the linker alone. For a complete PROTAC conjugate, in vivo studies are conducted following institutional guidelines. The compound is typically formulated using a vehicle containing DMSO, PEG300, Tween-80, and saline and administered via intraperitoneal (IP) or intravenous (IV) injection. The long PEG8 spacer may improve the pharmacokinetic properties of the conjugate by enhancing water solubility and reducing aggregation.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of approximately 825.90, a molecular formula of C42H55N3O14, and a standard purity of ≥98%. It appears as a solid at room temperature. For storage, it should be kept as a powder at -20degC for up to 3 years or in a solvent at -80degC for 6 months. It is soluble in DMSO and other organic solvents. The product should be stored in a cool, dry place, sealed, away from moisture. The DBCO group should be protected from light to prevent degradation. CAS: 2553412-88-5.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be observed during handling. The DBCO group is reactive and should be handled with care to avoid premature reaction with azides in the environment. The NHS ester is moisture-sensitive and should be handled in a dry environment. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license. This compound is not an approved drug and has not been cleared for clinical use.
|
| References |
[1]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562
|
| Additional Infomation |
The combination of a DBCO group (copper-free click chemistry) and an NHS ester on a long PEG8 spacer provides a versatile platform for constructing PROTACs under bioorthogonal conditions. The copper-free nature of SPAAC avoids the potential toxicity and side reactions associated with copper catalysts, making this linker ideal for conjugations in the presence of sensitive biomolecules or live cells. The NHS ester provides a versatile conjugation handle for attachment to any primary amine-containing molecule, including lysine residues on proteins and N-termini of peptides. The long PEG8 spacer provides a flexible, hydrophilic linker that can accommodate a wide range of distances between the target protein binding site and the E3 ligase recruitment site.
|
| Molecular Formula |
C42H55N3O14
|
|---|---|
| Molecular Weight |
825.90
|
| Exact Mass |
825.368
|
| CAS # |
2553412-88-5
|
| PubChem CID |
134159736
|
| Appearance |
Light yellow to yellow oil
|
| Density |
1.29±0.1 g/cm3(Predicted)
|
| LogP |
-0.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
32
|
| Heavy Atom Count |
59
|
| Complexity |
1320
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)N(C1=O)OC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCC(=O)N2CC3=CC=CC=C3C#CC4=CC=CC=C42
|
| InChi Key |
OALUNVCTIRHONS-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C42H55N3O14/c46-38(11-12-39(47)44-33-36-7-2-1-5-34(36)9-10-35-6-3-4-8-37(35)44)43-16-18-52-20-22-54-24-26-56-28-30-58-32-31-57-29-27-55-25-23-53-21-19-51-17-15-42(50)59-45-40(48)13-14-41(45)49/h1-8H,11-33H2,(H,43,46)
|
| Chemical Name |
(2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[2-[2-[2-[2-[[4-(2-azatricyclo[10.4.0.04,9]hexadeca-1(16),4,6,8,12,14-hexaen-10-yn-2-yl)-4-oxobutanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2108 mL | 6.0540 mL | 12.1080 mL | |
| 5 mM | 0.2422 mL | 1.2108 mL | 2.4216 mL | |
| 10 mM | 0.1211 mL | 0.6054 mL | 1.2108 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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